ISATUXIMAB for Multiple myeloma|Newly diagnosed multiple myeloma

Inclusion criteria

• {"criterion_text":"-1)\tMust be able to understand and voluntarily sign an informed consent form\n-10)\tAdequate organ function documented within one week prior to the first intake of investigational product (C1J1) defined as: o\tSerum total bilirubin < 2x upper limit of normal (ULN), o\tCreatinine clearance ≥ 30ml/min, calculated with MDRD formula, o\tSerum SGOT/AST or SGPT/ALT < 3x upper limit of normal (ULN).\n-11)\tSubjects affiliated with an appropriate social security system\n-12)\tA man who is sexually active with a pregnant woman or a woman of childbearing potential must agree to use a barrier method of birth control e.g., condom with spermicidal foam/gel/film/cream/suppository during the study and for at least 8 months after the last dose of treatment, even he has had a vasectomy\n-13)\tA female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: Not a female of childbearing potential Or \tA FCBP* who must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 – 14 days prior to and again within 24 hours prior to starting study medication and before each cycle of study treatment. A FCBP* must agree to continue abstinence from heterosexual intercourse or to use 2 reliable effective methods of contraception simultaneously without interruption: o\tFor at least 28 days before starting experimental treatments, o\tThroughout the entire duration of experimental treatments, o\tDuring dose interruptions, o\tAnd for at least 8 months after the last dose of experimental treatments.\n-14)\tAll patients must understand and accept to comply with the conditions of the lenalidomide pregnancy prevention plan\n-2)\tMust be able to adhere to the study visit schedule and other protocol requirements\n-3)\tLife expectancy of > 6 months\n-4)\tSubject, male or female, must be at least ≥ 65 years of age and < 80 years of age\n-5.\tNewly diagnosed multiple myeloma requiring therapy 5.1.\tMonoclonal plasma cells in bone marrow ≥ 10% or presence of biopsy-proven plasmacytoma 5.2.\tRevised International Myeloma Working Group diagnostic criteria for multiple myeloma\n-6)\tMust have measurable disease o IgG myeloma: M-protein ≥1.0 g/dL or urine M- protein≥200 mg/24 hours; or o\tIgA, IgM, IgD, or IgE multiple myeloma: serum M-protein ≥0.5 g/dL or urine M- protein ≥200 mg/24 hours; or o\tLight chain multiple myeloma: urine M- protein ≥200 mg/24 hours or Serum immunoglobulin free light chain ≥10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio\n-7)\tMust be non-transplant eligible and not frail o\tNewly diagnosed and not considered candidate for high-dose \tchemotherapy with SCT. o\tSubject must be not frail\n-8)\tperformance status ECOG ≤ 2\n-9)\tAdequate bone marrow function, documented within 72 hours and without transfusion 72 hours prior to the first intake of investigational product (C1J1) with no growth factor support (one week), defined as: o\tAbsolute neutrophils ≥ 1 x109/L, o\tUntransfused Platelet count ≥ 75 x109/L, o\tHemoglobin ≥ 8.5 g/dL."}

Exclusion criteria

• {"criterion_text":"-1\tSubject has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance, or smoldering multiple myeloma. Monoclonal gammopathy of undetermined significance is defined by presence of serum M-protein <3 g/dL; absence of lytic bone lesions, anemia, hypercalcemia, and renal insufficiency related to the M-protein; and (if determined) proportion of plasma cells in the bone marrow of 10% or less (Kyle 2003). Smoldering multiple myeloma is defined as asymptomatic multiple myeloma with absence of related organ or tissue impairment end organ damage (Kyle 2003, Kyle 2007).\n-10\tKnown to have hepatitis C active infection (positive HCV RNA and negative anti-HCV) Patients with antiviral therapy for HCV started before \tinitiation of IMP and positive HCV antibodies are eligible. The antiviral therapy for HCV should continue throughout the treatment period until seroconversion. Patients with positive anti-HCV and undetectable HCV RNA \twithout antiviral therapy for HCV are eligible.\n-11\tSubject has any clinically significant medical or psychiatric condition or disease (e.g., uncontrolled diabetes, acute diffuse infiltrative pulmonary disease) in the investigator’s opinion, would expose the patient to excessive risk or may interfere with compliance or interpretation of the study results.\n-12\tSubject has active systemic infection and severe infections requiring treatment with a parenteral administration of antibiotics.\n-13\t Subject has clinically significant cardiac disease, including: o\tmyocardial infarction within 6 months before randomization, or an unstable or uncontrolled disease/condition related to or affecting cardiac function (e.g., unstable angina, congestive heart failure, New York Heart Association Class III-IV) o\tuncontrolled cardiac arrhythmia (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] Version 5 Grade ≥2) or clinically significant ECG abnormalities or LVEF < 40 %\n-14\tSubject has known allergies, hypersensitivity, or intolerance to steroids, mannitol, pregelatinized starch, sodium stearyl fumarate, histidine (as base and hydrochloride salt), arginine hydrochloride, poloxamer 188, sucrose or any of the other components of study intervention that are not amenable to premedication with steroids and H2 blockers or would prohibit further treatment with these agents, monoclonal antibodies or human proteins, or their excipients\n-15\tKnown hypersensitivity, allergy to one of the study products (isatuximab, lenalidomide, bortezomib), dexamethasone or to one of the excipients\n-Acute diffuse infiltrative pneumopathy, pericardial disease\n-17\tSubject has plasma cell leukemia (according to World Health Organization [WHO] criterion: ≥20% of cells in the peripheral blood with an absolute plasma cell count of more than 2 × 109/L) or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).\n-18\tSubject is known or suspected of not being able to comply with the study protocol (e.g., because of alcoholism, drug dependency, or psychological disorder). Subject has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol- specified assessments. Subject is taking any prohibited medications\n-19\tSubject has had major surgery within 2 weeks before randomization or has not fully recovered from surgery, Kyphoplasty or vertebroplasty is not considered major surgery\n-2\tSubject has a diagnosis of Waldenström’s disease, or other conditions in which IgM M-protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions.\n-20\tSubject has received an investigational drug (including investigational vaccines) within 14 days or 5 half-lives of the investigational drug prior to initiation of study intervention, whichever is longer, or used an invasive investigational medical device within 4 weeks before randomization or is currently enrolled in an interventional investigational study. In case of very aggressive disease (i.e. circulating plasma cell) delay could be shortened after agreement between sponsor and investigator, in absence of residual toxicities from previous therapy\n-21\tRefusal to consent or protected by legal regime (under judicial protection, guardianship, trusteeship)\n-22\tSubject has contraindications to required prophylaxis for deep vein thrombosis and pulmonary embolism\n-23\tIncidence of gastrointestinal disease that may significantly alter the absorption of oral drugs\n-3\tSubject has prior or current systemic therapy or SCT for multiple myeloma, with the exception of an emergency use of a short course (equivalent of dexamethasone 40 mg/day for a maximum 4 days) of corticosteroids before treatment.\n-4\tSubject has a history of malignancy (other than multiple myeloma) within 3 years before the date of randomization (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the investigator, with concurrence with the Coordinator Investigator, is considered cured with minimal risk of recurrence within 3 years).\n-5\tSubject has had radiation therapy within 7 days of randomization unless done for antalgic reason or in case of functional risk for the patient\n-6\tSubject has had plasmapheresis within 7 days of randomization unless patient disease is still measurable (inclusion criteria n° 6) after the plasmapheresis\n-7 Subject is exhibiting clinical signs of meningeal involvement of multiple myeloma.\n-8\tSubject known to be seropositive for history of human immunodeficiency virus (HIV) or to have hepatitis A active infection.\n-9 Known to have hepatitis B active or uncontrolled infection (positive HBsAg and/or HBV DNA) o\tPatient can be eligible if anti-HBc IgG positive (with or without positive anti-HBs) but HBsAg and HBV DNA are negative. If anti-HBV therapy in relation with prior infection was started before initiation of IMP, the anti-HBV therapy and monitoring should continue throughout the study treatment period. o\t• Patients with negative HBsAg and positive HBV DNA observed during screening period will be evaluated by a specialist for start of anti-viral treatment: study treatment could be proposed if HBV DNA becomes negative and all the other study criteria are still met."}

Primary endpoints

• {"endpoint_text":"-MRD negative rate: defined as the proportion of patients with MRD negative in bone marrow aspirate (< 10-5) at 18 months","definition_or_measurement_approach":"Defined as the proportion of patients with MRD negative in bone marrow aspirate (< 10-5) at 18 months (bone marrow aspirate MRD measurement threshold 10^-5)."}

Secondary endpoints

• {"endpoint_text":"-Clinical and laboratory parameters, adverse events, and vital signs according to CTCAE 5.0","definition_or_measurement_approach":"Safety assessed by clinical and laboratory parameters, adverse events and vital signs graded per CTCAE v5.0."}
• {"endpoint_text":"-Overall Response rate defined as the proportion of patients with best overall response /VGPR or better rate defined as the proportion of patients with CR and VGPR /Duration of response defined as the time from first response to the date of first documentation of progression/Time to first response-time to best response defined as the time from randomization to the date of first documentation /Rate of primary refractory: defined as the proportion of patients with SD or DP","definition_or_measurement_approach":"Efficacy endpoints: Overall Response Rate = proportion with best overall response; VGPR or better rate = proportion with CR or VGPR; Duration of response = time from first response to documented progression; Time to first response/time to best response measured from randomization; Primary refractory rate = proportion with SD or DP."}
• {"endpoint_text":"-MRD rate: defined as the proportion of patients with MRD in bone marrow aspirate (< 10-5) at 12 months, and yearly","definition_or_measurement_approach":"MRD rate measured on bone marrow aspirate at threshold <10^-5 at 12 months and annually thereafter."}
• {"endpoint_text":"-Sustained MRD rate: defined as the proportion of patients with sustained MRD in bone marrow aspirate (< 10-5) between 2 evaluations as determined in the protocol.","definition_or_measurement_approach":"Sustained MRD defined as MRD negativity (<10^-5) sustained between two protocol-specified evaluations."}
• {"endpoint_text":"-Rate of loss of MRD at 10-5: defined as the proportion of patients with MRD negative at 10-5 who lose the MRD negative status at the next evaluation.","definition_or_measurement_approach":"Proportion of patients who were MRD negative at 10^-5 and convert to MRD positive at the following assessment."}
• {"endpoint_text":"-Time to reach MRD negative rate at 10-5: defined as the time from randomization to the date of the first MRD negative rate at 10-5 Time to lose MRD negative rate at 10-5: defined as the time from randomization or from the date of MRD negative at 10-5 to the date of MRD positive at 10-5","definition_or_measurement_approach":"Time-to-event endpoints measured from randomization to first MRD negativity (10^-5) and time to loss of MRD negativity measured from randomization or from date of MRD negative to date of MRD positive."}
• {"endpoint_text":"-OS=the time from the date of randomization to death TTP=the time from randomization to the date of 1er documentation of DP PFS= the time from randomization until the earliest date of documented DP or death TTNT= as time from discontinuation from treatment to the date of next myeloma therapy in patients that had progression and are alive. EFS=as permanent discontinuation of study treatment as a whole, death or progression .","definition_or_measurement_approach":"Standard time-to-event definitions: OS = time from randomization to death; TTP = time from randomization to first documentation of disease progression; PFS = time from randomization to documented progression or death; TTNT = time from treatment discontinuation to next myeloma therapy; EFS = permanent discontinuation of study treatment, death or progression."}
• {"endpoint_text":"-To determine Response, MRD rate and survival rate in either arm with regards to genomic abnormalities in the bone marrow tumor plasma cells","definition_or_measurement_approach":"Subgroup analyses of response, MRD rate and survival by genomic abnormalities in bone marrow tumour plasma cells as specified in protocol."}
• {"endpoint_text":"-All endpoints of efficacy of originator and generic bortezomib will be studying statistically","definition_or_measurement_approach":"Statistical comparison of efficacy endpoints between originator and generic bortezomib formulations."}
• {"endpoint_text":"-All endpoints of efficacy of originator and generic lenalidomid will be studying statistically","definition_or_measurement_approach":"Statistical comparison of efficacy endpoints between originator and generic lenalidomide formulations."}
• {"endpoint_text":"-All endpoints of apixaban exposure will be studying statistically","definition_or_measurement_approach":"Pharmacokinetic/exposure analyses for apixaban exposure to be statistically evaluated."}
• {"endpoint_text":"-All endpoints of correlation between apixaban plasma level and myeloma treatments will be studying statistically","definition_or_measurement_approach":"Correlation analyses between apixaban plasma levels and myeloma treatments."}
• {"endpoint_text":"-The outcome measure are: -\tAdverse events (arm A vs B) -\tOverall management of the Velcade therapy within the frame of BENEFIT -\tCost of the subsequent line of therapy (in both arms) -\tProgression in arm B of patients having relapsed before C19 (post C19 no more Velcade)Quality-adjusted life years (QALYs).","definition_or_measurement_approach":"Health economics and safety outcome measures including adverse events comparison, management of Velcade, cost of subsequent therapy lines, progression patterns and QALYs."}

France

Earliest CTIS Part Ii Submission Date

10-10-2024

Latest Decision Or Authorization Date

26-09-2025

Processing Time Days

351

Number Of Sites

58

Number Of Participants

270

Primary sponsor

Full Name

Centre Hospitalier Universitaire De Poitiers

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France

Third parties

• {"country":"","full_name":"CHU de Poitiers","duties_or_roles":"Source of monetary support (listed in CTIS 'sourceOfMonetarySupport')","organisation_type":""}
• {"country":"","full_name":"SANOFI","duties_or_roles":"Source of monetary support (listed in CTIS 'sourceOfMonetarySupport')","organisation_type":"Pharmaceutical company"}